We have recently demonstrated that liposomes accumulate in low flow myocardial infarct regions. One objective of this proposal is the study of the mechanisms of uptake of liposomes by ischemia or infarcted myocardium. We will also study the application of liposomes as carriers of therapeutic agents in experimental models of myocardial infarction and in vitro, in fetal mouse heart organ culture. Fetal mouse heart culture will permit the study of well controlled degrees of injury: anoxia, reversible and irreversible ischemia and situations of recovery. We will combine the use of radiotracers with light and electronmicroscopy to determine the type of cells responsible for liposome accumulation, the degree of damage needed to provoke such uptake, and the possibility of increasing uptake in infarct regions. Liposomes are demonstrated carriers of drugs; therefore, we also will study the pharmacodynamics of drug-liposomes complexes and evaluate myocardial responses to this new therapeutic modality. During the course of this project, we will attempt to deliver compounds within liposomes that until now have not been utilized therapeutically because of the impossibility of intracellular delivery (buffers) or because of the destruction of the substance when injected into the bloodstream (prostaglandins). Antiarrhythmic drugs will also be incorporated into liposomes to increase delivery to low flow infarct regions which may be the major site of arrhythmogenesis. Therapeutic efficiency in this instance will be monitored by assessment of regional refractory periods.